The goal of this application is to support my professional development as a clinical investigator and successful mentor to junior faculty and fellows in patient-oriented research My research focus has been to investigate the effects of nutritional status on neuroendocrine function, and as such, I have used HIV disease as a relevant disease model, with two funded NIH R01 grants for which I am the PI. The three Specific Aims of this grant stem from a significant body of work accomplished over the past few years demonstrating hypogonadism in HIV-infected women and a severe insulin resistance pattern in HIV-infected patients with lipodystrophy In these funded studies, I will investigate the mechanisms of androgen deficiency and also the effects of long-term physiologic testosterone replacement in this population Furthermore, I will study the mechanisms of insulin resistance, investigating the critical role of increased lipolysis and the effects of thiazolidinediones in this population The grant for the first Specific Aim, to study the effects of androgens in HIV-infected women, will expire at the end of this year, and a follow-up proposal, recently submitted will further investigate adrenal androgen shunting and DHEA in this population Preliminary data in this regard show a novel effect of HIV on adrenal metabolism, with shunting toward cortisol and away from androgen production The grant for the third Specific Aim is funded until 2005 I have had good success as a mentor, with two recent K-23 awardees and six former or current trainees There has been significant interest in my research from Endocrine Fellows and also from Fellows in Harvard Nutrition Division The Institutional Environment at the MGH, with a strong and diverse Endocrine Division, GCRC, and Center for AIDS Research is outstanding The Department of Medicine has made a substantial commitment toward my development as a clinical researcher responsible for training a large number of fellows However, it is clearly necessary to reduce my clinical activities in order to devote sufficient time to the training and mentoring of junior faculty and fellows The Mid-career Investigator Award in Patient Oriented Research is an ideal mechanism to ensure the necessary support to reduce clinical and administrative responsibilities, and ensure my continued success as a mentor and clinical researcher.